Inflammatory mechanisms linking maternal and childhood asthma

Abstract

Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness, inflammation, and remodeling. Asthma often develops during childhood and causes lifelong decrements in lung function and quality of life. Risk factors for childhood asthma are numerous and include genetic, epigenetic, developmental, and environmental factors. Uncontrolled maternal asthma during pregnancy exposes the developing fetus to inflammatory insults, which further increase the risk of childhood asthma independent of genetic predisposition. This review focuses on the role of maternal asthma in the development of asthma in offspring. We will present maternal asthma as a targetable and modifiable risk factor for childhood asthma and discuss the mechanisms by which maternal inflammation increases childhood asthma risk. Topics include how exposure to maternal asthma in utero shapes structural lung development with a special emphasis on airway nerves, how maternal type‐2 cytokines such as IL‐5 activate the fetal immune system, and how changes in lung and immune cell development inform responses to aero‐allergens later in life. Finally, we highlight emerging evidence that maternal asthma establishes a unique “asthma signature” in the airways of children, leading to novel mechanisms of airway hyperreactivity and inflammatory cell responses.

Association of the Risk of Childhood Asthma at Age 6 With Maternal Allergic or Immune-Mediated Inflammatory Diseases: A Nationwide Population-Based Study

“…Genetic and epigenetic backgrounds are significant in the development of childhood asthma. Maternal asthma serves as a risk factor of childhood asthma because of maternal inflammation-related type-2 cytokines activating the fetal immune system during pregnancy ( 36 ). The risk of childhood asthma is higher in mothers with different pregnancy conditions, including asthma history, allergy, chronic bronchitis, and severe stress ( 37 ).…”

Early Sensory and Temperament Features in Infants Born to Mothers With Asthma: A Cross-Sectional Study

“…Importantly, such perinatal outcomes confer a higher risk for poor developmental outcomes for infant offspring such as more challenging temperament, greater sensory processing difficulties, increased hyperactivity/inattention, social/peer problems, and developmental delays (Dudova et al, 2014;Guerra et al, 2014;Oudgenoeg-Paz et al, 2017;Cassiano et al, 2020). Children whose mothers have asthma are also at high risk of developing asthma themselves (Lebold et al, 2020), particularly if their mother's asthma was not managed effectively during pregnancy (Liu et al, 2018). Despite these known risks for adverse outcomes, there is a paucity of research investigating the early behavioural development of infants born to mothers with asthma.…”

Association between maternal ritodrine hydrochloride administration during pregnancy and childhood wheezing up to three years of age: The Japan environment and children's study

“…36 The biological mechanism of MRA on childhood wheezing remains unclear; the underlying mechanism regarding the MRAassociated childhood wheezing may be associated with pathological impairment in the trachea of children, hyper-responsiveness, and beta-receptor desensitization. [37][38][39] As maternal inflammation increases the risk of childhood asthma via maternal type-2 cytokines in maternal asthma cases, 40 IUI, which frequently coexists in mothers with PTL, may affect the incidence of childhood wheezing by changing the maternal and the child's inflammatory condition.…”